EFFECT OF SEPSIS ON LIPID METABOLISM

脓毒症引起的碳水化合物和蛋白质代谢的改变是 详细描述，但脂代谢的异常很差 明白了。脓毒症时引起高甘油三酯血症的机制 仍然不为人知。这可能是由于甘油三酯产量增加所致。 通过肝脏，通过脂蛋白脂肪酶减少外周清除，和/或 肝脏分泌率增加。 这项研究将确定和描述负责的机制(S) 革兰氏阴性脓毒症时脂代谢的改变。脂类的变化 新陈代谢将通过测量体内的血脂、合成 肝脏和脂肪组织中脂质类的比率，活性 脂蛋白脂酶、肝脏造脂酶、甘油三酯比率 脓毒症大鼠的分泌和清除以及胰岛素和胰升糖素水平 模特。肝脏的作用将通过在 新鲜分离的肝细胞体外合成脂类的研究 禁食脓毒症大鼠和禁食对照组大鼠。辨别食物的影响 限制和败血症对脂类代谢、脂类合成的影响 在灌胃喂养的大鼠的分离肝细胞中测量。这个 在分离的肝细胞中观察到的脂质合成异常将 利用分离株的原代培养进行进一步研究 肝细胞。这些关于原代培养的实验将定义 不同底物对脂肪合成恢复时间的影响 胰岛素的存在或不存在对脂质合成的影响 细胞外因子(S)进行交叉研究。肝细胞来源 用脓毒症大鼠血清和正常大鼠血清孵育正常大鼠和脓毒症大鼠。 拟议的研究将阐明高甘油三酯血症的机制。 脓毒症，有望成为开发更好营养的基础 对败血症患者的支持。

The sepsis-induced alterations in carbohydrate and protein metabolism are described in detail, yet the abnormalities in lipid metabolism are poorly understood. The mechanism causing hypertriglyceridemia during sepsis remains unknown. This could result from increased triglyceride production by the liver, reduced peripheral removal by lipoprotein lipase, and/or an increase in liver secretion rate. This study will identify and describe the mechanism(s) responsible for the altered lipid metabolism during gram-negative sepsis. The changes in lipid metabolism will be assessed by measuring in vivo serum lipids, synthesis rates of the lipid classes in liver and adipose tissue, activities of lipoprotein lipase, the liver lipogenic enzymes, rates of triglyceride secretion and clearance, and insulin and glucagon levels in a septic rat model. The role of the liver will be evaluated further by determining in vitro synthesis of the lipid classes in freshly isolated hepatocytes from fasted septic and fasted control rats. To distinguish the effects of food restriction and sepsis on lipid metabolism, lipid synthesis will be measured in isolated hepatocytes from intragastrically-fed rats. The observed abnormalities of lipid synthesis in the isolated hepatocytes will be investigated further by using primary cultures of the isolated hepatocytes. These experiments with the primary culture will define the recovery time of lipid synthesis, the effect of different substrates in the presence or absence of insulin on lipid synthesis, and the presence of extracellular factor(s) by performing cross-over studies. Hepatocytes from normal and septic rats are incubated with septic rat serum and normal serum. The proposed studies will clarify the mechanism of hypertriglyceridemia in sepsis and hopefully serve as a basis for developing better nutritional support for the septic patient.